Lipidic poly(2-oxazoline)s as PEG replacement steric stabilisers for cubosomes

Hypothesis: Cubosomes are promising delivery vehicles for a wide range of drugs and biomolecules. Polymers such as the polyethylene glycol (PEG)-based Pluronic F-127 have been widely used for dispersing and stabilising lipid cubosomes. However, due to the PEG-immunogenicity, and pre-existing anti-PEG antibodies in some individuals, the efficacy of PEG-stabilised nanomedicines has been reduced. In this study, we hypothesise that lipidic poly(2-oxazoline)s have the potential to stabilise cubosomes, which can be used to encapsulate a hydrophobic drug similar to cubosomes stabilised with F-127. Experiments: Two lipidic polymers consisting of an oleyl (OA) chain connected to a poly(2-methyl-2-oxazoline) backbone were synthesised using cationic ring-opening polymerisation (PMeOx₄₀-OA and PMeOx₈₀-OA). The PMeOx_n-OA stabilised monoolein cubosomes were compared to F-127 cubosomes in particle size, stability, mesophase structure, and biocompatibility. Findings: The obtained PMeOx_n-OA were well-defined (low dispersity) and had a high degree of OA functionalisation (≥95%). These polymers were as good as F-127 in producing well dispersed monoolein cubosomes and maintained the internal cubic structure. The cubosomes stabilised with PMeOx_n-OA showed lower cytotoxic effect compared to F-127 stabilised cubosomes against OVCAR-3 cells. Furthermore, the PMeOx_n-OA cubosomes significantly improved the solubility of SN-38, a poorly water-soluble cancer drug.